Title |
Crystal structure of human LC8 bound to a peptide from Ebola virus VP35 |
Author |
Dahwan Lim1,2, Ho-Chul Shin1, Joon Sig Choi2, Seung Jun Kim1, and Bonsu Ku1 |
Address |
1Disease Target Structure Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea, 2Department of Biochemistry, Chungnam National University, Daejeon 34134, Republic of Korea |
Bibliography |
Journal of Microbiology, 59(4),410–416, 2021,
|
DOI |
10.1007/s12275-021-0641-7
|
Key Words |
LC8, Ebola virus, EBOV, VP35, crystal structure,
LC8-binding motif |
Abstract |
Zaire ebolavirus, commonly called Ebola virus (EBOV), is an
RNA virus that causes severe hemorrhagic fever with high
mortality. Viral protein 35 (VP35) is a virulence factor encoded
in the EBOV genome. VP35 inhibits host innate immune
responses and functions as a critical cofactor for viral
RNA replication. EBOV VP35 contains a short conserved
motif that interacts with dynein light chain 8 (LC8), which
serves as a regulatory hub protein by associating with various
LC8-binding proteins. Herein, we present the crystal structure
of human LC8 bound to the peptide comprising residues
67−76 of EBOV VP35. Two VP35 peptides were found to
interact with homodimeric LC8 by extending the central β-
sheets, constituting a 2:2 complex. Structural analysis demonstrated
that the intermolecular binding between LC8 and
VP35 is mainly sustained by a network of hydrogen bonds
and supported by hydrophobic interactions in which Thr73
and Thr75 of VP35 are involved. These findings were verified
by binding measurements using isothermal titration calorimetry.
Biochemical analyses also verified that residues 67−76
of EBOV VP35 constitute a core region for interaction with
LC8. In addition, corresponding motifs from other members
of the genus Ebolavirus commonly bound to LC8 but with
different binding affinities. Particularly, VP35 peptides originating
from pathogenic species interacted with LC8 with
higher affinity than those from noninfectious species, suggesting
that the binding of VP35 to LC8 is associated with
the pathogenicity of the Ebolavirus species. |